LAST WEEK TODAY!

A summary of what was published on ProstateWarriors.com during the past week

Hello fellow warriors! Another promising week for us! Stay strong and fight on!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• Phase 2 Trial: ENV105 Combined with Apalutamide in mCRPC
  ENV105 (carotuximab) is a monoclonal antibody targeting CD105, an endothelial protein whose expression increases as prostate cancer develops resistance to androgen-receptor (AR) therapies. In an ongoing Phase 2 trial, ENV105 is combined with apalutamide in men with metastatic castration-resistant prostate cancer (mCRPC) who previously failed an AR inhibitor. Early interim efficacy data from eight evaluable patients demonstrated a median progression-free survival (PFS) exceeding 13 months, substantially surpassing the trial’s benchmark goal of 6.7 months. Five of the eight patients remained on treatment without disease progression, and seven of nine evaluated patients achieved PSA declines.​
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• Phase 2 Trial: Terbinafine Drug Repurposing for Biochemically Recurrent Prostate Cancer
  ​The randomized Phase 2 TerbinaPro trial is evaluating terbinafine, a widely available, low-cost oral antifungal drug, in men with biochemically recurrent prostate cancer. Terbinafine targets squalene epoxidase (SQLE), a key enzyme in intracellular cholesterol synthesis that is overexpressed in aggressive prostate cancer and helps sustain androgen receptor signaling. Preclinical studies showed that inhibiting SQLE with terbinafine reduced cholesterol production inside cancer cells, weakened AR activity, and slowed tumor growth, including in enzalutamide- or abiraterone-resistant models, without lowering systemic blood cholesterol levels. The trial will evaluate whether terbinafine can delay PSA progression and induce significant PSA reductions.​
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• Phase 2 Trial: JNJ-101556143 (HLD-0915) RIPTAC in Treatment-Resistant mCRPC
  ​A new Phase 2 trial will evaluate JNJ-101556143 (HLD-0915), an oral Regulated Induced Proximity Targeting Chimera (RIPTAC), in approximately 100 men with treatment-resistant mCRPC. Rather than attempting to block AR signaling directly, the molecule uses full-length AR on prostate cancer cells as an anchor to bring the essential protein BRD4 into a lethal complex, triggering cell death. Interim Phase 1/2 human data showed a 42% PSA50 response rate across 31 heavily pretreated patients (rising to 59% in patients completing at least two cycles) and partial responses in all five patients with measurable disease.​
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• Phase 1 Trial: JUR-003 Bispecific T-Cell Engager for Metastatic Prostate Cancer
  ​A first-in-human Phase 1 trial is enrolling up to 210 patients to evaluate JUR-003 across cohorts with mCRPC, metastatic hormone-sensitive prostate cancer (mHSPC), and oligometastatic disease. Evidence connects JUR-003 to EM1031, a bispecific T-cell engager targeting KLK2 and CD3 that physically bridges T cells to KLK2-positive prostate cancer cells to trigger immune killing. In preclinical xenograft models, the compound achieved complete tumor eradication while generating lower cytokine release than clinical-stage reference engagers.
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Preclinical Research & Reviews

• Bipolar Androgen Therapy as a Sensitizer for PARP Inhibitors
  ​A 2026 review outlines how Bipolar Androgen Therapy (BAT),rapid cycling between high and low testosterone levels, can make prostate cancer more vulnerable to PARP inhibitors. BAT induces substantial DNA damage and downregulates homologous recombination repair genes, creating a temporary “BRCAness-like” stateeven in tumors lacking classic BRCA1/2 mutations. This concept is supported by a Phase 2 trial of BAT combined with olaparib in mCRPC, which showed clinical activity in both HRR-mutated and HRR-proficient patients.​
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• Targeting the BUB1B–CENP-E Pathway in Enzalutamide-Resistant Prostate Cancer
  ​Research in Cancer Research identified the mitotic protein BUB1B and its downstream regulator CENP-E as key vulnerabilities in enzalutamide-resistant prostate cancer. Lowering BUB1B levels impaired cancer cell division, whereas BUB1B elevation promoted growth under hormone deprivation. Using GSK-923295, a clinical-stage CENP-E inhibitor, researchers successfully disrupted this pathway, resensitizing resistant prostate cancer cells to enzalutamide and significantly slowing tumor progression in mouse models.​
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• Neuromedin U as an Immune Evasion Mechanism in Neuroendocrine Prostate Cancer
  ​A study published in Oncogene uncovered a mechanism by which aggressive neuroendocrine prostate cancer hides from the immune system via Neuromedin U (NMU). NMU is highly expressed in AR-negative, neuroendocrine-positive metastases and stimulates neutrophils to produce S100A9, which suppresses tumor-infiltrating CD8+ T cells. Inhibiting the NMU/S100A9 axis restored CD8+ T-cell entry into tumors, slowed cancer growth in preclinical models, and enhanced the efficacy of immune checkpoint therapy.​
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• B7-H3 Signaling and Dual Inhibition in Castration-Resistant Prostate Cancer
  ​A study in Cancer Discovery demonstrated that B7-H3 does more than serve as a surface marker; it actively drives immune suppression via MAPK signaling in myeloid-derived suppressor cells. When B7-H3 is blocked, tumors adapt by releasing SPINK1, which activates cancer-associated fibroblasts via the EGFR–MEK–ERK pathway to protect the tumor. Combining a B7-H3 antibody with the MEK inhibitor trametinib effectively shut down this escape route, yielding durable tumor control in preclinical mCRPC models.​
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• Modular “Plug-and-Play” meCAR-T Cell Platform for Solid Tumors
  ​A study in Cancer Immunology Research introduced meditope-enabled CAR-T (meCAR-T) cells, which feature a molecular docking site that binds externally administered adapters after cell infusion. This “plug-and-play” architecture allows doctors to redirect the same CAR-T cells toward different tumor antigens (such as PSMA, STEAP1, or PSCA) or supply additional functional signals over time without manufacturing a new batch of cells. This platform directly targets solid tumor heterogeneity, with Phase 1 solid tumor trials currently in preparation.​
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And…that’s all folks! For today at least!
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Have a great weekend!

Max